Chronic Obstructive Pulmonary Disease (COPD) is a generic designation of diseases such as bronchitis and pulmonary emphysema. According to the World Health Organization (WHO), currently it ranks the fourth place of the cause of death. Concerning the COPD, a root pathological condition thereof is extremely complicated and contains large majority of unknown clinical states, and even radical therapeutic agent does not exist. In this century, it is feared to rapidly increase the number of the COPD patients on a global scale due to increased number of smokers and atmospheric pollutions caused by industrial developments in developing countries, and therefore an establishment of a rapid and simple detection method becomes an overarching imperative.
Hydrolytic processing of sputum, blood, urine of a COPD patient is conducted and the obtained samples are analyzed with Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS) to provide observations of desmosine, which serves as a crosslinking amino acid of an elastic fiber elastin controlling an expansion and a contraction of a lung alveolus and is represented by the following formula (5), and isodesmosine, which is an isomer thereof and is shown in the following formula (6). Desmosines are expected as promising biomarkers for COPD, since the quantity thereof existing in a COPD patient is distinctive as compared with that of a healthy person.

Technologies related to a total synthesis of desmosine are described in Toyonobu Usuki, and other 7 authors, “Total synthesis of COPD biomarker desmosine that crosslinks elastin”, Chem. Commun., 2012, Vol. 48, pp. 3233 to 3235, and, Hiroto Yanuma, and another author, “Total synthesis of the COPD biomarker desmosine via Sonogashira and Negishi cross-coupling reactions”, Tetrahedron Lett., 2012, Vol. 53, pp. 5920 to 5922.
Technology related to a synthetic process of compounds having pyridine ring is described in Li-Bing Yu and other 4 authors, “Lanthanide-Promoted Reactions of Aldehydes and Amine Hydrochlorides in Aqueous Solution. Synthesis of 2,3-Dihydropyridinium and Pyridinium Derivatives”, J. Org. Chem., 1997, Vol. 62, pp. 208 to 211.